Genetically Thin? CD38 enzyme is necessary for diet-induced obesity

by: Fagan Jeremy
Date: July 2007

Obesity is a growing health problem in our current society that puts increase the risk of diabetes, heart disease and stroke diagnosis. A lifestyle that includes a high fat diet is often a main contributor to the development of obesity, but researchers at the Mayo Clinic College of Medicine and Harvard Medical School have found a protein required for diet-induced obesity.

"Obesity is a complex problem compounded by multiple factors, one of which is our genes, said Eduardo Chini, M.D., Ph.D., an anesthesiologist at Mayo Clinic.

Chini and his colleagues determined that a CD38 protein that is normally involved with energy metabolism is required for diet-induced obesity.

"Genes play a role in about 50 percent of cases, and in this study, we demonstrate that CD38 regulates body weight," said Chini.

The novel part of the research was that when the expression of the CD38 is eliminated and a high fat diet is consumed, there is no significant weight gain.

The method of studying role of a specific protein is often done by eliminating the gene that codes for that specific protein or "knocking it out" of the mice genome. The creation of knockout mice has made the study of specific genes much easier and applicable to human disorders, such as obesity.

The CD38-knockout mice and a regular wild type mice were put on a diet were 60% of their caloric intake was from fats. After 4 weeks of the diet and lack of exercise, the wild type had a much higher percentage of body fat and glucose intolerance when compared to the CD38 knockout mice, which had no weight gain and adverse reactions to glucose. This shows significant evidence that the CD38 enzyme is necessary for diet-induced obesity.

The anti-obesity mechanism behind the CD38 knockout mice was a significant increase in energy expenditure or usage. It was also found that without the CD38 enzyme, a cascade involved with the regulation of energy creation and expenditure and growth and maintenance of the cell powerhouse, the mitochondria, regulates metabolism and protects against obesity.

Future research will look at the quality of life and life span of the mice and CD38 role as sensor and regulator of metabolism.

- By Jeremy Fagan.

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